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Introduction: Therapeutic Apheresis Effects on Medications

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Introduction: Therapeutic Apheresis Effects on Medications Introduction: Therapeutic apheresis effects on medications AABB/ASFA Joint Session Suzanne Thibodeaux, MD PhD Assistant Professor Department of Pathology and Immunology Washington University in St. Louis October 14, 2018 Financial disclosures None www.aabb.org 2 Learning objectives By the end of the talk, the audience should be able to: 1. Describe the basic principles of therapeutic apheresis 2. Identify apheresis attributes that may affect medication levels 3. Identify patient attributes that may affect medication levels www.aabb.org 3 www.aabb.org 4 https://www.google.com/search?q=apheresis&ie=utf-8&oe=utf-8&client=firefox-b-1-ab What is apheresis? According to the American Society for Apheresis A procedure in which blood of the patient or donor is passed through a medical device which separates one or more components of blood and returns the remainder with or without extracorporeal treatment or replacement of the separated component. 5 Schwartz, et al. Journal of Clinical Apheresis 31:149–162 (2016) Where did apheresis come from? Cream separators and computer companies! 1870s 1940s-1950s 1960s Cream separator - hand-cranked WW2 – isolation of serum albumin IBM –development of automated continuous centrifugation fraction from plasma, other apheresis, IBM 2990 separation of blood components Dr. Karl de Laval Dr. Edwin Cohn George Judson http://worldapheresis.org/wp-content/uploads/2015/07/CDLposter.png; https://www-03.ibm.com/ibm/history/exhibits/healthcare/healthcare_08.html The apheresis circuit is continuous Adapted from: Williams ME, Balogun RA. Clin J Am Soc Nephrol. 2014;9(1):181-190. Apheresis separates whole blood into its components Specific gravity Blood Component <1.025 Density Plasma 1.030 Plasma Platelets WBC RBC 1.035 1.040 Platelets Plasma Density 1.045 Immature hematopoietic cells 1.050 T cells Platelets 1.055 Lymphocytes Plasma 1.060 B cells Promyelocytes 1.065 WBC Monocytes WBC 1.070 Myelocytes, Basophils 1.075 Band and Segmented Neutrophils RBC RBC Reticulocytes 1.080 1.085 1.090 Erythrocytes 1.095 >1.100 https://www.terumobct.com/Public/306670988.pdf 8 Araujo AB, et al. Cytotherapy. 2017 Jan;19(1):128-130.; Keever-Taylor C, et al. Blood 2014 124:3850; Adapted from: Linz, W. et al. (2014). Principles of Apheresis Technology (5th ed.) Vancouver, British Columbia: ASFA. Apheresis =/ Hemodialysis Arterial Venous inflow return Membrane Dialysate Dialysate outflow inflow https://www.niddk.nih.gov/health-information/kidney-disease/kidney-failure/hemodialysis https://www.uptodate.com/contents/overview-of-the-hemodialysis-apparatus?source=search_result&search=hemodialysis&selectedTitle=1~150 Learning objectives By the end of the talk, the audience should be able to: 1. Describe the basic principles of therapeutic apheresis Apheresis allows density-based separation of blood into components that can then be removed/replaced 2. Identify apheresis attributes that may affect medication levels 3. Identify patient attributes that may affect medication levels www.aabb.org 10 Apheresis enables removal or exchange of selected blood components Specific gravity Blood Component <1.025 Plasma Plasma Exchange 1.030 Adsorption, 1.035 LDL apheresis 1.040 Platelets Plateletpheresis 1.045 Immature hematopoietic cells 1.050 T cells 1.055 Plasma Lymphocytes 1.060 B cells Leukapheresis Promyelocytes 1.065 WBC Monocytes 1.070 Myelocytes, Basophils Extracorporeal 1.075 Band and Segmented Neutrophils photopheresis RBC 1.080 Reticulocytes 1.085 Red Blood Cell 1.090 Erythrocytes exchange 1.095 >1.100 11 Araujo AB, et al. Cytotherapy. 2017 Jan;19(1):128-130.; Keever-Taylor C, et al. Blood 2014 124:3850; Adapted from: Linz, W. et al. (2014). Principles of Apheresis Technology (5th ed.) Vancouver, British Columbia: ASFA. Schwartz, et al. J Clin Apheresis 31:149–162 (2016) 12 Araujo AB, et al. Cytotherapy. 2017 Jan;19(1):128-130.; Keever-Taylor C, et al. Blood 2014 124:3850; Adapted from: Linz, W. et al. (2014). Principles of Apheresis Technology (5th ed.) Vancouver, British Columbia: ASFA. Kinetics of antibody removal during therapeutic plasma exchange 100 Before 80 After 60 40 20 0 Percent antibody antibody remaining Percent 1 2 3 4 Number of Plasma exchanges Roman PEF, et al. Curr Opin Anesthesiol 2014, 27:57–64. Adapted from: Kaplan AA. Am J Disease 2008; 52:1180-96. Immune Adsorption and LDL apheresis Antibody or LDL Adsorption column www.aabb.org 14 https://www.accessdata.fda.gov/cdrh_docs/pdf12/H120005C.pdf. https://www.therapeutic-apheresis.com/en/therapies/immunoadsorption/. Schwartz, et al. J Clin Apheresis 31:149–162 (2016) 15 Araujo AB, et al. Cytotherapy. 2017 Jan;19(1):128-130.; Keever-Taylor C, et al. Blood 2014 124:3850; Adapted from: Linz, W. et al. (2014). Principles of Apheresis Technology (5th ed.) Vancouver, British Columbia: ASFA. Schwartz, et al. J Clin Apheresis 31:149–162 (2016) 16 Araujo AB, et al. Cytotherapy. 2017 Jan;19(1):128-130.; Keever-Taylor C, et al. Blood 2014 124:3850; Adapted from: Linz, W. et al. (2014). Principles of Apheresis Technology (5th ed.) Vancouver, British Columbia: ASFA. Schwartz, et al. J Clin Apheresis 31:149–162 (2016) 17 Araujo AB, et al. Cytotherapy. 2017 Jan;19(1):128-130.; Keever-Taylor C, et al. Blood 2014 124:3850; Adapted from: Linz, W. et al. (2014). Principles of Apheresis Technology (5th ed.) Vancouver, British Columbia: ASFA. Apheresis enables removal or exchange of selected blood components Specific gravity Blood Component <1.025 Plasma Plasma Exchange 1.030 Adsorption, 1.035 LDL apheresis 1.040 Platelets Plateletpheresis 1.045 Immature hematopoietic cells 1.050 T cells 1.055 Plasma What aboutLymphocytes 1.060 B cells Leukapheresis Promyelocytes 1.065 WBC Monocytes 1.070 Myelocytes, Basophils Extracorporeal 1.075 Band and Segmented Neutrophils photopheresis RBCmedications?! 1.080 Reticulocytes 1.085 Red Blood Cell 1.090 Erythrocytes exchange 1.095 >1.100 18 Araujo AB, et al. Cytotherapy. 2017 Jan;19(1):128-130.; Keever-Taylor C, et al. Blood 2014 124:3850; Adapted from: Linz, W. et al. (2014). Principles of Apheresis Technology (5th ed.) Vancouver, British Columbia: ASFA. Learning objectives By the end of the talk, the audience should be able to: 1. Describe the basic principles of therapeutic apheresis Apheresis allows density-based separation of blood into components that can then be removed/replaced 2. Identify apheresis attributes that may affect medication levels Apheresis can have varying effects on remove blood components and medications within a given layer 3. Identify patient attributes that may affect medication levels www.aabb.org 19 Patient factors with potential effects on apheresis and medications Apheresis Medications Patient size/plasma volume Determines amount of replacement fluid used May determine dosing Adjustment of weight-based BMI/amount of adipose tissue Adjustment of calculations dosing Dictates frequency, duration, replacement Disease requiring apheresis Disease-specific medications fluid used, amount processed, etc. May affect anticoagulant used, replacement Comorbidities dose adjustments fluid, replacement volume Clinical status May affect replacement fluid, access Altered metabolism Hypalbuminemia – may affect Nutritional status Hypoalbuminemia, electrolyte abnormalities protein-bound drugs www.aabb.org 20 Learning objectives By the end of the talk, the audience should be able to: 1. Describe the basic principles of therapeutic apheresis Apheresis allows density-based separation of blood into components that can then be removed/replaced 2. Identify apheresis attributes that may affect medication levels Apheresis can have varying effects on remove blood components and medications within a given layer 3. Identify patient attributes that may affect medication levels Patient factors can influence both apheresis and medications, and the intersection between can be complex www.aabb.org 21 Thank you! www.aabb.org 22 Anticoagulants & Apheresis: The Lab Medicine & Blood Bank Perspective Christopher A. Tormey, MD Associate Professor of Laboratory Medicine Yale University School of Medicine VA Connecticut Healthcare System October, 2018 Talk Outline Discussion of the various types of anticoagulation, their mechanism of action, basic lab monitoring, and half-lives Also discuss ‘safe’ hold periods prior to central line placement for non-urgent procedures Review of how apheresis-related care (particularly plasma exchange) is impacted by these various forms of anticoagulation from the BB perspective Removal + considerations for replacement fluids Anticoagulants: Overview on Mechanism of Action Anticoagulants, which exploit the mechanisms of normal hemostasis, come in essentially one of four varieties: Agents to induce factor depletion Focus on For example, warfarin these classes for Agents that inhibit coagulation factor activity today’s talk For example, heparin Agents that inhibit PLT function For example, aspirin Clot ‘busters’ For example, tissue plasminogen activator (tPA) Yale-VA CT IR BB Guideline FACTOR DEPLETION Warfarin Anticoagulation Following the ingestion of warfarin, a vitamin K antagonist (VKA), all vitamin K dependent factors will begin to decrease fVII = most sensitive to warfarin therapy because of it’s very short in vivo half-life (4-6 hours) Anticoagulant effect may not be seen until several doses (or until many hours after dosing) Since fVII is very sensitive to warfarin, we use the PT to gauge efficacy of therapy Goal PT = 1.5-2x upper limit of normal for most hypercoagulable or treated patients Equates to INRs of
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